EPEN-27. CDKN2A DELETION IN SUPRATENTORIAL EPENDYMOMA WITH RELA ALTERATION INDICATES A DISMAL PROGNOSIS – A RETROSPECTIVE ANALYSIS OF THE HIT EPENDYMOMA TRIAL COHORT. (4th December 2020)

• Record Type: Journal Article
• Authors: Jünger, Stephanie T; Andreiuolo, Felipe; Mynarek, Martin; Dörner, Evelyn; zur Mühlen, Anja; Velez-Char, Natalia; von Hoff, Katja; Rutkowski, Stefan; Warmuth-Metz, Monika; Kortmann, Rolf-Dieter; Timmermann, Beate; von Bueren, Andre O; Pietsch, Torsten
• Is Part Of: Neuro-oncology. Volume 22(2020)Supplement 3
• Page Start: iii313
• Page End: iii313
• Publication Date: 2020-12-04
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa222.164
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: INTRODUCTION: Since supratentorial RELA -fusion positive ependymomas are considered a biologically distinct disease, we aimed to identify histological and genetic predictors of outcome in a defined cohort of pediatric patients. MATERIALS AND METHODS: We analyzed 54 RELA ependymomas in pediatric patients treated according to HIT2000-E protocols. All cases underwent central neuropathological review. Genome-wide copy number alterations were assessed by molecular inversion probe or SNP array. RELA alterations were detected by RT-PCR, sequencing and assessment of nuclear p65-RelA protein. Copy number alteration of the CDKN2A (cyclin dependent kinase inhibitor 2A ) locus and concordant p16 protein expression were analyzed. RESULTS: Fifty-two tumors were classified as WHO-grade III (96.3%) with high mitotic activity in 39 cases (72.2%), vascular proliferation in 47 (87.0%), necrosis in 43 (79.6%) and clear cell morphology in 19 (35.2%). All tumors harbored RELA alterations. Homo- or heterozygous CDKN2A deletions were detected in 9 (16.7%) and 14 (25.9%) cases, respectively. p16 protein expression was lost in all cases with homozygous deletion. Median follow-up was 5.4 years with 5-years EFS and OS of 74.1% and 92.6%. In Kaplan-Meier analysis high mitotic activity was related to shorter EFS (p=0.016) and clear cell morphology to longer OS (p=0.039); CDKN2A deletion was associated with shorter OS (homozygous deletion, p=0.009; homo-or heterozygous deletion, p=0.034). No correlation between CDKN2A deletion and high mitotic activity was found but with higher age at diagnosis (p=0.001). CONCLUSION: Deletion of CDKN2A occurred in 42.6% of supratentorial ependymomas with RELA alteration and represented a genetic predictor of worse overall outcome in pediatric patients.